A Novel, Circulating Tumor Cell Enrichment Method Reduces ARv7 False Positivity in Patients with Castration-Resistant Prostate Cancer

Takehiko Nakasato; Chiho Kusaka; Mika Ota; Yuki Hasebe; Kumiko Ueda; Tsutomu Unoki; Kazuhiko Oshinomi; Jun Morita; Yoshiko Maeda; Takeshi Shichijo; Michio Naoe; Yoshio Ogawa

doi:10.3390/diagnostics10030151

Diagnostics (Mar 2020)

A Novel, Circulating Tumor Cell Enrichment Method Reduces ARv7 False Positivity in Patients with Castration-Resistant Prostate Cancer

Takehiko Nakasato,
Chiho Kusaka,
Mika Ota,
Yuki Hasebe,
Kumiko Ueda,
Tsutomu Unoki,
Kazuhiko Oshinomi,
Jun Morita,
Yoshiko Maeda,
Takeshi Shichijo,
Michio Naoe,
Yoshio Ogawa

Affiliations

Takehiko Nakasato: Department of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan
Chiho Kusaka: Department of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan
Mika Ota: Department of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan
Yuki Hasebe: Department of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan
Kumiko Ueda: Department of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan
Tsutomu Unoki: Department of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan
Kazuhiko Oshinomi: Department of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan
Jun Morita: Department of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan
Yoshiko Maeda: Department of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan
Takeshi Shichijo: Department of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan
Michio Naoe: Department of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan
Yoshio Ogawa: Department of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan

DOI: https://doi.org/10.3390/diagnostics10030151
Journal volume & issue: Vol. 10, no. 3
p. 151

Abstract

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Background: The AR-V7 splice variant is a cause of castration-resistant prostate cancer (CRPC). However, testing for the presence of AR-V7 by real-time polymerase chain reaction (RT-PCR) shows AR-V7 positivity in healthy individuals. We hypothesized that the positivity reflects contamination by hematopoietic cells. We tried a novel circulating tumor cell (CTC) enrichment instrument, using Celsee, to clear hematopoietic cells. Methods: We tested whole blood or Celsee-enriched samples for AR-V7 by RT-PCR, and included samples from 41 CRPC patients undergoing sequential therapy. We evaluated the associations between AR-V7 status and clinical factors. We evaluated factors affecting AR-V7 positivity. Results: AR-V7 positivity was lower in Celsee-enriched than in whole blood specimens. AR-V7 and clinical factors did not predict the therapy effectiveness. We found no significant differences in the effectiveness of enzalutamide/abiraterone (Enz/Abi) upon AR-V7 evaluation. All AR-V7 positive patients had resistance to Enz/Abi. Docetaxel (DTX), cabazitaxel (CBZ), and Radium223 treatment showed no significant difference in the treatment effectiveness, regardless of AR-V7 presence. AR-V7 was more frequently positive than Extent of disease (EOD) 2 in cases with bone metastases. Conclusion: Celsee CTC enrichment suppresses AR-V7 false positivity. All AR-V7 positive patients presented resistance to Enz/Abi. DTX, CBZ, and Radium223 were effective and remain treatment options. AR-V7 positivity should progressively appear in patients with advanced bone metastases.

Published in Diagnostics

ISSN: 2075-4418 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Medicine (General)
Website: http://www.mdpi.com/journal/diagnostics

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